This interdisciplinary project intends to bring a biomedical engineering approach to the field of drug abuse. The goals of the proposed research are to develop a biosensing methodology to improve drug screening diagnostics. Nano-structured porous silicon (PSi)is an ideal material for biosensing due to its inexpensive fabrication, intrinsic optical and filtering properties, and compatibility with array and microfluidic technologies. These properties of PSi offer advantages over current screening technologies by its potential for uncomplicated high-throughput analysis at point-of-care (POC). The amount of bound target within a PSi immunosensor is related to its refractive index. Changes in the refractive index are monitored using an optical reader. Long term goals are to achieve visual color change readout for clinicians at POC. The first aim will focus on developing a semi-quantitative screening assay in PSi. A competitive binding assay will target opiates in urine as a proof of concept. Studies will analyze assay cross-reactivity with opiates of similar structure and quantify non-specific binding from unrelated drugs and interferents present in negative urine specimens. Results from the PSi biosensor will be compared to standard clinical laboratory results for opiate screens in patient urine specimens. The second aim of the proposed work will incorporate the competitive binding assay worked out in Aim 1 into a bioactive hydrogel-PSi sensor composite device which can be developed into future sweat patch applications. The prototype design of the hydrogel-sensor composite will be used to detect opiates in aqueous solution for proof of concept of its drug screening potential. The direct optical readout of PSi sensors would reduce complicated and destructive processing (extraction) of current sweat patches and allow for POC screening. Using PSi sensors in such different formats as urinalysis and sweat patch screening highlights its versatility as a drug biosensing methodology. Optimization of design characteristics and analysis of assay binding properties in both aims will include fluorescent microscopy, Enzyme-Linked ImmunoSorbent Assay liters, scanning electron microscopy, and UV-vis spectrometry in addition to PSi optical detection. Methodologies developed here could be extended to detect many other small molecules and drug classes. 7 The new drug screening methods developed by this research have the potential to be used at point of care, bypassing the cost and time associated with sending specimens out for laboratory testing. Ultimately this would also benefit the patient by providing doctors with results at the specific time of treatment.